This project will investigate alterations of regional cerebral blood flow (rCBF) that occur during hyperglycemia. Hyperglycemia is a pathologic condition occuring in poorly controlled diabetics, but may also occur in nondiabetics during illness or as the result of medical treatment. The presence of hyperglycemia prior to stroke or cardiac arrest is associated with increased risk and extent of irreversible brain injury. Also, hyperglycemia may cause abnormalities of brain function, as in the clinical syndrome of hyperosmolar coma. However, little is known about the effect of hyperglycemia on rCBF in humans or laboratory animals. Accordingly, this research plan is designed to describe the fundmental changes that occur in rCBF during chronic and acute hyperglycemia in awake restrained rats. Regional cerebral blood flow will be measured using the diffusible indicator iodoantipyrine. Hyperglycemia will be induced acutely by intraperitoneal injection of glucose and chronically by intravenous injection of streptozotocin. The dose-response effect and the time course of rCBF changes induced by acute hyperglycemia will be measured. The role of plasma osmolarity and blood viscosity in producing rCBF changes will be evaluated using mannitol as a control treatment. Also, the relationship between the metabolic rate of glucose consumption and CBF during hyperglycemia will be determined. This study will describe a basic physiologic mechanism of CBF control and establish ground work for further study of hyperglycemic CBF alteration in animal models of brain ischemia.